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Investigating multimorbidity trajectories in people living with MASLD diagnosis: A trajectory analysis using the UK
Fang Lu1,2, Hailin Yang1,2, Bingyang She1,2
1Phase I Clinical Trial Research Ward, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, People's Republic of China.
Background:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern, and its presence increases the risk of multi-system diseases. This study aimed to investigate the multimorbidity trajectories of chronic diseases in people living with MASLD.
Methods:
We identified 137 859 MASLD patients in UK Biobank and used 'propensity score matching' to match an equal number of non-MASLD controls. Diseases were reclassified into 472 categories based on the International Classification of Diseases, Tenth Revision (ICD-10) chapters. Multimorbidity trajectories post-MASLD diagnosis were mapped using validated trajectory analysis. We introduced the 'Multimorbidity Trajectory Position Index (MTPI)' to denote a disease's position across trajectories, highlighting its temporal pattern.
Results:
Participants had a median age of 59 (52-64) years, with 65.6% being male. Over 13 years of follow-up, Phenome-wide association analysis (PheWAS) identified 128 diseases with elevated risks post-MASLD diagnosis, with obesity (HR: 8.77, 95% CI: 8.37-9.18), diabetes (HR: 4.34, 95% CI: 4.15-4.53), and sleep disorders (HR: 3.21, 95% CI: 3.01-3.42) showing the strongest associations. Trajectory analysis revealed 6637 common trajectories involving 69 diseases, grouped into metabolic, inflammatory, and cardiovascular clusters. These clusters are linked to downstream conditions, with intermediary diseases such as hypertension, diabetes, and inflammatory arthritis, ultimately leading to electrolyte imbalances and sepsis. MTPI demonstrated a gradient in disease progression, with early-stage conditions showing low values, mid-stage conditions moderate values, and late-stage conditions high values.
Conclusion:
People living with MASLD demonstrated multimorbidity trajectories involving co-occurrence of metabolic diseases, chronic inflammation, and cardiovascular diseases. If replicated, these pathways may serve as promising targets to improve late-life health in individuals with MASLD.
Insights
Metabolic dysfunction-associated steatotic liver disease (MASLD) patients develop multiple chronic diseases over time, including obesity, diabetes, and cardiovascular conditions. Understanding these multimorbidity trajectories may help target interventions to improve long-term health outcomes.
Area of Science:
- Hepatology and Metabolic Diseases
- Chronic Disease Epidemiology
- Multimorbidity Research
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health issue linked to increased risks of various systemic diseases.
- MASLD significantly elevates the risk of developing multiple chronic conditions, impacting overall health and longevity.
Purpose of the Study:
- To investigate the complex patterns and progression of chronic diseases in individuals diagnosed with MASLD.
- To map the multimorbidity trajectories and identify key diseases associated with MASLD over time.
Main Methods:
- Utilized UK Biobank data to identify 137,859 MASLD patients and matched them with non-MASLD controls using propensity score matching.
- Employed trajectory analysis and the Multimorbidity Trajectory Position Index (MTPI) to map disease progression and temporal patterns.
- Classified diseases into 472 categories using ICD-10 codes for comprehensive phenome-wide association analysis (PheWAS).
Main Results:
- Phenome-wide association analysis identified 128 diseases with increased risk post-MASLD diagnosis, notably obesity, diabetes, and sleep disorders.
- Trajectory analysis revealed distinct clusters of co-occurring diseases: metabolic, inflammatory, and cardiovascular, progressing through intermediary conditions like hypertension and arthritis.
- The MTPI effectively demonstrated disease progression, differentiating early, mid, and late-stage conditions.
Conclusions:
- Individuals with MASLD exhibit characteristic multimorbidity trajectories involving metabolic, inflammatory, and cardiovascular disease clusters.
- These identified disease pathways present potential therapeutic targets for improving the long-term health and well-being of MASLD patients.
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